This invention relates to a class of strategically substituted 1,2-benzisoxazoles with antiinflammatory, antipyretic and analgesic activity prepared from cyclodehydration of corresponding salicylaldoximes with an isocyanate under unexpectedly mild conditions.
Although the first 1,2-benzisoxazoles were prepared almost a century ago, they had not been made from salicylaldoximes employing an isocyanate as the cyclodehydration reagent until the present invention. In fact, according to K. H. Wunsch and A. J. Boulton in "Advances in Heterocyclic Chemistry," Vol. 8, Academic Press, New York and London, 1967, Pg, 283, "salicylaldoxime itself does not give 1,2-benzisoxazoles directly."
Since 1,2-benzisoxazoles are usually quite sensitive to both heat and base, and earlier syntheses generally required pyrolysis or alkaline decomposition, the scope of their derivatization, as well as the exploration of their pharmaceutical usages has been far from complete. It is with the newly discovered method of the present invention that many new derivatives of 1,2-benzisoxazole are made available for pharmaceutical studies including tests for antiinflammatory, antipyretic, and analgesic activities.
In recent years, non-steroidal antiinflammatory agents have been sought after to circumvent the undesirable side effects of steroidal agents. It is, therefore, an object of the present invention to provide new 1,2-benzisoxazoles of novel structures.
It is also an object of the present invention to provide a novel process for the preparation of these novel antiinflammatory, antipyretic and analgesic agents.
A further object of this invention is to provide a novel method of treating pain, fever and inflammation by administration of the novel compounds of this invention to a patient.
Finally an object of this invention is to provide novel pharmaceutical compositions comprising one or more of the novel compounds of this invention as active ingredient.